Functional evidence for retinal adenosine receptors.

Abstract

Adenosine is a potent modulator of various physiological functions. Although adenosine receptors have been demonstrated in the retina, little is known about their functional role. This study determined the effects of relatively selective adenosine agonists on K+ depolarization-induced release of dopamine and retinal arteriolar tone. For dopamine release studies, bovine retinas were isolated and endogenous synaptosomal stores were loaded with [3H] dopamine. Retinas were then transferred to a superfusion chamber and the spontaneous and K+ depolarization-induced release of dopamine were determined. Cyclopentyladenosine (CPA) did not significantly alter the spontaneous release of dopamine; however, CPA produced a dose-related inhibition of K+ depolarization-evoked release of dopamine. This CPA-induced suppression of dopamine release was reversed by pretreatment with the adenosine A1 antagonist cyclopentyltheophylline. In retinal vasculature studies, adenosine and its agonists injected intravitreally dilated retinal arterioles and venules, in newborn pigs, with a potency profile indicative of mediation by A2 adenosine receptors. Intravitreal injections of drugs inhibiting the metabolism of endogenous adenosine also induced an arteriolar vasodilation which was inhibited by co-administration of an adenosine receptor antagonist. Intravitreally administered adenosine antagonists also attenuated the vasodilative response to both systemic hypoxia and systemic hypotension in the newborn pig, indicating that endogenously produced adenosine is important in retinal blood flow regulation.